Evolution of Clinical Outcome Measures and Biomarkers in Sporadic Adult-Onset Degenerative Ataxia.

Background: Sporadic adult-onset ataxias without known genetic or acquired cause are subdivided into multiple system atrophy of cerebellar type (MSA-C) and sporadic adult-onset ataxia of unknown etiology (SAOA).

Objectives: To study the differential evolution of both conditions including plasma neurofilament light chain (NfL) levels and magnetic resonance imaging (MRI) markers.

Methods: SPORTAX is a prospective registry of sporadic ataxia patients with an onset >40 years.

Health economic analysis of patients treated with isavuconazole in a German comprehensive cancer centre.

Background: Invasive fungal diseases (IFD) are life-threatening and demand timely and appropriate treatment. Research showed that isavuconazole treatment positively affects clinical outcome and length of hospital stay (LOS).

Objectives: The aim of this study was to assess the hospital costs of patients diagnosed with IFD and treated with isavuconazole using real-world data from a German cancer centre.

Membrane-bound IL-2 improves the expansion, survival, and phenotype of CAR Tregs and confers resistance to calcineurin inhibitors.

Background: Regulatory T cells (Tregs) play an important role in the maintenance of immune homeostasis and the establishment of immune tolerance. Since Tregs do not secrete endogenous IL-2, they are especially dependent on external IL-2. IL-2 deficiency leads to lower Treg numbers, instability of the Treg phenotype and loss of immune regulation.

The Role of G Protein-Coupled Receptor Kinase 6 Regulation in Inflammation and Pain.

The G protein-coupled receptor kinase 6 is associated with inflammation and pathological pain. Impairment of GRK6 expression was described in chronic inflammatory diseases such as rheumatoid arthritis and this was shown to be accompanied by an imbalance of downstream signaling pathways. Here, we discuss novel aspects of GRK6 interaction and its impact upon hyperalgesia and inflammatory processes.

Last Resort Antibiotics Costs and Reimbursement Analysis of Real-Life ICU Patients with Pneumonia Caused by Multidrug-Resistant Gram-Negative Bacteria in Germany.

Multidrug-resistant Gram-negative bacteria (MDR-GNB) cause serious infections and aggravate disease progression. Last resort antibiotics are effective against MDR-GNB and are reimbursed by flat rates based on German diagnosis-related groups (G-DRG). From a hospital management perspective, this analysis compared hospital reimbursement for last resort antibiotics with their acquisition costs to outline potential funding gaps.

Diagnostic Cardiac CT for the Improvement of Cardiovascular Event Prediction.

Background: The aim of the long-term Heinz Nixdorf Recall Study (observation period 20 years) was to establish the extent to which computed tomography (CT) improves the predictability of cardiovascular events relative to determination of risk factors alone.

Methods: In the period 2000-2003, study staff examined 4355 probands (53% of them female) aged 45-75 years with no signs of cardiovascular disease. The Atherosclerotic Cardiovascular Disease (ASCVD) score was calculated on the basis of demographic data and cardiovascular risk factors.

Next Generation Sequencing of Free Microbial DNA for Rapid Identification of Pathogens in Critically Ill Children with Systemic Inflammatory Response Syndrome (SIRS).

Background: Infections, major surgeries, and hyperinflammatory syndromes are known to trigger Systemic Inflammatory Response Syndrome (SIRS). Discrimination between infectious and noninfectious inflammation often poses a challenge in chronically ill patients with multiple comorbidities. These patients are routinely treated with a variety of anti-infective medications before a pathogen is identified.

Efficacy and Safety of N-Acetyl-l-Leucine in Children and Adults With GM2 Gangliosidoses.

Background And Objectives: GM2 gangliosidoses (Tay-Sachs and Sandhoff diseases) are rare, autosomal recessive, neurodegenerative diseases with no available symptomatic or disease-modifying treatments. This clinical trial investigated N-acetyl-l-leucine (NALL), an orally administered, modified amino acid in pediatric (≥6 years) and adult patients with GM2 gangliosidoses.

Methods: In this phase IIb, multinational, open-label, rater-blinded study (IB1001-202), male and female patients aged ≥6 years with a genetically confirmed diagnosis of GM2 gangliosidoses received orally administered NALL for a 6-week treatment period (4 g/d in patients ≥13 years, weight-tiered doses for patients 6-12 years), followed by a 6-week posttreatment washout period.

The Architecture of Macular Neovascularizations Predicts Treatment Responses to Anti-VEGF Therapy in Neovascular AMD.

Introduction: Anti-VEGF therapy is an effective option for improving and stabilizing the vision in neovascular age-related macular degeneration (nAMD). However, the response to treatment is markedly heterogeneous. The aim of this study was therefore to analyze the vascular characteristics of type 1,2, and 3 macular neovascularizations (MNV) in order to identify biomarkers that predict treatment response, especially with regard to changes in intraretinal and subretinal fluid.

New Wound Management of Driveline Infections with Cold Atmospheric Plasma.

The use of ventricular assist devices as a bridge to transplant or as destination therapy has increased. Wound complications increase morbidity in this cohort. Cold atmospheric plasma is a source of reactive oxygen and nitrogen species and can reduce the microbial load in skin wounds without negative effects on the surrounding tissue.

A multi-omics machine learning framework in predicting the recurrence and metastasis of patients with pancreatic adenocarcinoma.

Local recurrence and distant metastasis are the main causes of death in patients with pancreatic adenocarcinoma (PDAC). Microbial content in PDAC metastasis is still not well-characterized. Here, the tissue microbiome was comprehensively compared between metastatic and non-metastatic PDAC patients.

Novel Ga-FAPI PET/CT Offers Oncologic Staging Without COVID-19 Vaccine-Related Pitfalls.

In the setting of ongoing coronavirus disease 2019 vaccination, vaccine-related tracer uptake in locoregional lymph nodes has become a well-known issue in tumor staging by F-FDG PET/CT. Ga-fibroblast-activation protein inhibitor (FAPI) PET/CT is a new oncologic imaging tool that may overcome this limitation. We assessed postvaccine head-to-head and same-day F-FDG and Ga-FAPI-46 PET/CT findings in a series of 11 patients from a large, prospective imaging registry.

Fear of Death during COVID-19 Does Not Explain Post-Infection Depression Symptoms beyond Reported Symptoms during the Infection in COVID-19 Survivors.

The COVID-19 pandemic poses an unprecedented global burden to the general population and, in particular, to individuals who have been infected with SARS-CoV-2. In the context of the discussion about "post COVID-19", the aim of the study was to advance research on mental health and long-term consequences after COVID-19. In total, 214 COVID-19 survivors (female: 54.

The frequency of non-motor symptoms in SCA3 and their association with disease severity and lifestyle factors.

Background: Non-motor symptoms (NMS) are a substantial burden for patients with SCA3. There are limited data on their frequency, and their relation with disease severity and activities of daily living is not clear. In addition, lifestyle may either influence or be affected by the occurrence of NMS.

Progressive Spinal Cord Degeneration in Friedreich's Ataxia: Results from ENIGMA-Ataxia.

Background: Spinal cord damage is a hallmark of Friedreich's ataxia (FRDA), but its progression and clinical correlates remain unclear.

Objective: The objective of this study was to perform a characterization of cervical spinal cord structural damage in a large multisite FRDA cohort.

Methods: We performed a cross-sectional analysis of cervical spinal cord (C1-C4) cross-sectional area (CSA) and eccentricity using magnetic resonance imaging data from eight sites within the ENIGMA-Ataxia initiative, including 256 individuals with FRDA and 223 age- and sex-matched control subjects.

Wound Infections in Adult Patients after Berlin Heart EXCOR Biventricular Assist Device Implantation.

The Berlin Heart EXCOR is a paracorporeal, pulsatile ventricular assist device used in patients of all age groups. However, adolescent and adult patients on EXCOR support are scarcely explored. Herein, we present a detailed description of infectious complications in this patient cohort.

The role of the basal ganglia and cerebellum in adaptation to others' speech rate and rhythm: A study of patients with Parkinson's disease and cerebellar degeneration.

Background: Spoken language is constantly undergoing change: Speakers within and across social and regional groups influence each other's speech, leading to the emergence and drifts of accents in a language. These processes are driven by mutual unintentional imitation of the phonetic details of others' speech in conversational interactions, suggesting that continuous auditory-motor adaptation takes place in interactive language use and plasticity of auditory-motor representations of speech persists across the lifespan. The brain mechanisms underlying this large-scale social-linguistic behavior are still poorly understood.

Farnesoid X receptor agonist tropifexor attenuates cholestasis in a randomised trial in patients with primary biliary cholangitis.

Background & Aims: The safety, tolerability, and efficacy of the non-bile acid farnesoid X receptor agonist tropifexor were evaluated in a phase II, double-blind, placebo-controlled study as potential second-line therapy for patients with primary biliary cholangitis (PBC) with an inadequate ursodeoxycholic acid response.

Methods: Patients were randomised (2:1) to receive tropifexor (30, 60, 90, or 150 μg) or matched placebo orally once daily for 28 days, with follow-up on Days 56 and 84. Primary endpoints were safety and tolerability of tropifexor and reduction in levels of γ-glutamyl transferase (GGT) and other liver biomarkers.

Framework and baseline examination of the German National Cohort (NAKO).

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19-74 years were recruited and examined in 18 study centres in Germany.

Cancer care in German centers of excellence during the first 2 years of the COVID-19 pandemic.

Purpose: An increasing number of international studies demonstrate serious negative effects of the COVID-19 pandemic on the timely diagnosis of cancer and on cancer treatment. Our study aimed to quantitatively and qualitatively evaluate the capacities of German Comprehensive Cancer Centers (CCCs) in different areas of complex oncology care during the first 2 years of the COVID-19 pandemic.

Methods: Prospective panel survey over 23 rounds among 18 CCCs in Germany between March 2020 and June 2022.

Diagnostic performance of tomosynthesis, digital mammography and a dedicated digital specimen radiography system versus pathological assessment of excised breast lesions.

Background: The aim of the study was to compare the performance of full-field digital mammography (FFDM), digital breast tomosynthesis and a dedicated digital specimen radiography system (SRS) in consecutive patients, and to compare the margin status of resected lesions versus pathological assessment.

Patients And Methods: Resected tissue specimens from consecutive patients who underwent intraoperative breast specimen assessment following wide local excision or oncoplastic breast conservative surgery were examined by FFDM, tomosynthesis and SRS. Two independent observers retrospectively evaluated the visibility of lesions, size, margins, spiculations, calcifications and diagnostic certainty, and chose the best performing method in a blinded manner.

Strengthening Altitude Knowledge: A Delphi Study to Define Minimum Knowledge of Altitude Illness for Laypersons Traveling to High Altitude.

Berendsen, Remco R., Peter Bärtsch, Buddha Basnyat, Marc Moritz Berger, Peter Hackett, Andrew M. Luks, Jean-Paul Richalet, Ken Zafren, Bengt Kayser, and the STAK Plenary Group.